Marfan syndrome, new mutations of the FBN1 gene

Abstract

Introduction: Marfan syndrome (SM) is a systemic disorder caused by mutations in the extracellular matrix protein fibrillin 1 (FBN1). With a dominant autosomal pattern, penetrance near 100% and variable expressivity. It has an incidence of 2-3 cases per 10.000 individuals; the patients are characterized by presenting ocular, cardiovascular and skeletal compromise. It has been suggested that the intrafamilial and interfamilial phenotypic variability, typical   of the syndrome, occurs by the association of other mutations called driver mutations. The SM diagnosis is based on a set of clinic and genetic criteria called Ghent nosology.

Objectives: Contribute with an SM case with a mutation in the fibrilin 1 gene not described previously; analyze the role of this new mutation and the driver mutations, besides showing the clinical utility of the Ghent nosology.  

Clinical case: Male patient with tall stature, myopia, personal history of Mitral valve prolapse, bilateral hindfoot deformity and suspected SM familiar history.   

Conclusion: Marfan syndrome is a systemic disorder of connective tissue characterized by a variable clinical spectrum. Even though there is a clear genetic causation, the recent descriptions of driver mutations, modifiers of the classical mutations´s phenotypic expression, are not yet fully elucidated. However it seems to suggest that in first-degree relatives of SM patients with no relevant phenotypic findings should be performed molecular diagnostic tests to accordingly establish genetic counseling.      

Key words: Marfan syndrome, Codon nonsense, FBN1, Driver mutations.